羟基磷灰石-β-环糊精复合微球的合成与性能

Synthesis and performance of hydroxyapatite-β-cyclodextrin composite microspheres

羟基磷灰石(hydroxyapatite,HA)是一种应用较为广泛的载药材料,将HA与相关材料复合制成载药微球可较好缓解药物突释现象.本研究以十二烷基磺酸钠(sodium dodecyl sulfonate,SDS)和脯氨酸(proline,Pro)作为模板剂,通过水热沉淀法合成碳酸钙微球,再通过水热法以离子交换方式将具有空腔结构的HA与β-环糊精(β-cyclodextrin,β-CD)进行复合,探究合成条件变化对微球的形貌影响,成功制备出形貌良好、分散性好、性能优良的HA-β-CD复合微球,使用X射线衍射、扫描电子显微镜和紫外可见分光度计等测试方法对所制备样品进行分析和表征,再以姜黄素作为负载药物进行载药性能测试,对载药量和包封率两个主要指标进行对比分析,同时对HA-β-CD微球在体外药物释放实验中的表现进行分析探究.结果表明,当β-CD质量分数在20%~30%、水热反应时间为6 h时,所制得的HA-β-CD复合微球的形貌良好,分散性好,复合微球的粒径主要分布在6.4~13.9μm,粒径大小均匀且具有空腔结构.载药性能测试结果表明,β-环糊精的掺入可以有效提升复合微球的药物包封效率和载药量,当β-环糊精质量分数为30%时,复合微球的载药量达到5.03%±0.37%,包封率达到37.67%±1.37%.药物体外释放性能测试结果显示,合成的HA-β-CD复合微球能明显缓解传统HA载药微球的突释现象,延长药物作用时间,具备良好的缓释性能.同时,对载药微球的形成机理及细胞毒性进行分析探讨,结果表明,HA-β-CD载药复合微球通过HA、β-CD及药物三者包合形成,可实现药物延迟释放,明显改善载药微球的缓释性能,且测试结果证明,HA-β-CD复合微球对细胞增殖几乎没有毒性.制备的HA-β-CD复合微球改善了纯HA载药微球易突释、载药量低和作用时间短等问题,具备良好的医用价值和应用潜力.

Hydroxyapatite(HA)is a widely used drug loading material,and combining HA with related materials to form drug loaded microspheres can effectively alleviate the phenomenon of drug burst release.For this purpose,the synthesis was involved using sodium dodecyl sulfonate(SDS)and proline(Pro)as templates through a hydrothermal precipitation method to create calcium carbonate microspheres.Subsequently,these microspheres were combined withβ-cyclodextrin via ion exchange in a hydrothermal process to create a cavity structure.The effects of varying synthesis conditions on the microsphere morphology were investigated.The results showed that when the content of cyclodextrin was 20%-30%and the hydrothermal reaction time was 6 h,HA-β-CD composite microspheres had well-defined morphology and good dispersion.Characterization using X-ray diffraction,scanning electron microscope,UV-Vis spectrophotometer confirmed the uniform particle size distribution(6.4-13.9μm)and presence of cavity structures in the HA-β-CD microspheres.Drug loading studies using curcumin as a model drug demonstrated that HA-β-CD microspheres achieved enhanced the drug loading capacity(5.03%±0.37%)and encapsulation efficiency(37.67%±1.37%)whenβ-cyclodextrin content was optimized at 30%.Vitro drug release tests indicated sustained release behavior,effectively mitigating burst release observed in traditional HA microspheres,thereby prolonging the drug efficacy.At the same time,the formation mechanism and cytotoxicity of drug loaded microspheres were analyzed and explored.The results showed that HA-β-CD drug loaded composite microspheres were formed through the encapsulation of HA,β-CD,and drugs,which can achieve delayed drug release and significantly improve the sustained release performance of drug loaded microspheres.Moreover,the test results showed that HA-β-CD composite microspheres have almost no toxicity to cell proliferation.HA-β-CD composite microspheres address limitations of drug-loaded pure HA microspheres such as rapid drug release,low drug loading,short duration of action,highlighting their significant medical value and application potential.